Latent patients with erectile dysfunction increases as the population ages and, considering the advent of an aging society in near future, attention has been concentrated on the significance of improving the quality of life (QOL) of patients by treatment. As a therapeutic agent, a cyclic GMP (cGMP)-specific phosphodiesterase (PDE) inhibitor, especially PDE-V inhibitor is used.
A therapeutic agent for erectile dysfunction preferably exerts the drug efficacy immediately after taking the agent so that the sexual response can be regulated on demand. However, some PDE-V inhibitors are known to show marked decrease in solubility in the neutral and alkaline regions compared to the acidic region. For example, the solubility of sildenafil citrate is 2.52 mg/ml at pH 1.2, while it is only 0.11 mg/ml at pH 6.8 (WO00/20033, page 4).
Thus, such a PDE-V inhibitor, when administered to a subject who just finished eating or is suffering from anacidity, would not dissolve well in the digestive tract, resulting in the delay of expression of efficacy and/or reduction of bioavailability (BA). For example, even Viagra (Pfizer) which is a rapid-acting tablets of sildenafil citrate, it has been reported that one should take the preparation about 1 hour in advance of the time when the efficacy is expected to be expressed (WO00/24383, page 2).
Examples of known PDE-V inhibitor-containing preparations for oral administration include intraoral quickly disintegrating tablets (JP-A 10-298062) prepared by a process comprising subjecting a mixture containing sildenafil citrate and a bondable disintegrant to wet granulation followed by compression molding, and granules coated with flavor mask (WO98/30209) wherein a core containing sildenafil citrate is coated with an inner coating layer of hydroxypropylcellulose and an outer coating layer of Eudragit-E 100 (gastric-soluble polymer). However, these preparations are directed to the improvement of disintegration of tablets or masking of bitterness and is irrelevant to the improvement of the solubility of PDE-V inhibitor itself.
There are also described tablets immediately disintegrating in the oral cavity (WO00/20033) wherein the solubility of PDE-V inhibitor is improved, which have been prepared by mixing a PDE-V inhibitor (sildenafil, phthaladine derivatives, etc.) with sugars, kneading together with a solvent and compressing under pressure. However, the preparations do not show sufficiently accelerated expression of drug efficacy as expected.